tbuckley/cabot-search huggingface dataset:
Abstract 9588: Intraplaque Myeloperoxidase Activity is a Hallmark of Vulnerable Atherosclerosis and Correlates With Clinical Outcomes
Authors: James Nadel, Sergey Tumanov, Stephanie Kong, Weiyu Chen, Vanathi Sivasubramaniam, Nicola Gianotti, Imran Rashid, Martin Ugander, Andrew Jabbour, Roland Stocker
Journal: Circulation (2022)

Introduction: There remains limited means by which to detect unstable atherosclerosis in patients at risk of myocardial infarction and stroke. Myeloperoxidase (MPO) is increased in unstable plaque and causally linked to plaque destabilization and rupture in pre-clinical models. We sought to assess whether MPO activity is greater in vulnerable human carotid and coronary atheroma, and how this relates to adverse cardiovascular events and non-invasive imaging parameters. Methods: Carotid endarterectomy specimens (CEA) were collected from 31 patients. Coronary trees were collected from 12 patients undergoing heart transplantation for ischemic cardiomyopathy. MPO activity was assessed through the conversion of hydroethidine added to tissue sections to the MPO-specific adduct 2-chloroethidium (2-Cl-E + ) and quantified by mass spectrometry. MPO activity was then compared with histologic determination of plaque phenotype and clinical outcomes. MPO activity was additionally assessed in high and low attenuation plaques derived by computed tomography, as well as perivascular adipose tissue (PVAT). Results: Unstable CEA had higher MPO activity when compared with stable CEA plaques (n = 26, 4.2 ± 3.1 vs. 0.2 ± 0.3 μmol/mgp; p &lt; 0.0001). Similar results were seen in coronary segments with unstable compared to stable plaque (n = 17, 0.6 ± 0.5 vs. 0.0 ± 0.0 μmol/mgp; p = 0.0006). When comparing MPO activity in CEA to clinical outcomes, asymptomatic and stroke-free patients had lower MPO activity compared to those with symptoms or ipsilateral stroke on neuroimaging (n = 12, 3.7 ± 2.1 vs. 0.1 ± 0.2 μmol/mgp; p = 0.002). CT-determined plaque attenuation did not identify plaque MPO activity (n = 30, 0.1 ± 0.1 vs. 0.2 ± 0.3 μmol/mgp; p = 0.23) and enzymatically active MPO was not found in PVAT. Conclusion: MPO is active within unstable human carotid and coronary plaques and correlates with symptomatic carotid disease and stroke. In addition, current non-invasive imaging parameters do not selectively identify plaques enriched with active MPO. As intraplaque MPO appears to be a hallmark of unstable atherosclerosis and can potentially be imaged non-invasively, further investigation into its potential utility as a diagnostic tool for high-risk atherosclerosis is warranted.
Abstract 304: Cerebral Near-infrared Spectroscopy During Pediatric In-hospital Cardiac Arrest: A Multicenter, Observational Study
Authors: IVIE ESANGBEDO, Prakadeshwari Rajapreyar, Matthew Kirschen, Dana Niles, Sangmo Je, Alexis A Topjian, Vinay M Nadkarni, Tia T Raymond
Journal: Circulation (2022)

Introduction: Cerebral regional oxygen saturation (crS0 2 ) measured by near-infrared spectroscopy (NIRS) during CPR is associated with outcomes in adults, but there is limited pediatric data. Hypothesis: Median crSO 2 during pediatric in-hospital cardiac arrest (IHCA) is associated with return of spontaneous circulation (ROSC) and survival to hospital discharge (SHD). Methods: Pediatric IHCA events from 2015-2022 with ≥ 1min CPR and intra-arrest crS0 2 reported by 3 sites in the pediRES-Q registry were included. ROSC was defined as return of spontaneous circulation for ≥ 20 mins without ECMO. We analyzed the association of ROSC for all events and SHD for index events only with median crS0 2 and percent crS0 2 measurements above a priori thresholds during 1) the entire event, 2) the first 5 mins, and 3) the final 5 mins by Fisher’s exact test, Wilcoxon rank sum test, and multivariable logistic regression with Firth bias correction. Results: There were 106 IHCA events in 81 patients. Median age was 0.3 yrs [0.06,0.85], 43% had cyanotic heart disease, and SHD in 61% (49/81). For all events, median CPR duration was 8 mins [3.25, 32] and ROSC was achieved in 62% (66/106). Higher median crSO 2 for the entire event, the first 5 mins, and the last 5 mins was significantly associated with ROSC and SHD (Table). Events with ROSC had significantly higher percent crS0 2 measurements ≥ 30% and 40% for the entire event. Patients with SHD had significantly higher percent crSO 2 measurements ≥ 30%, 40%, 50%, and 60% for the entire event (Table). Multivariable analysis controlling for age (aOR 1.02 [CI 1.01,1.05] p=0.012) and cyanotic heart disease (aOR 1.03 [CI 1.01,1.05] p=0.008) showed median crS0 2 was independently associated with ROSC. Conclusions: Higher median crSO 2 (measured by cerebral NIRS) during pediatric IHCA was significantly associated with increased rate of ROSC and SHD. Studies evaluating intra-arrest cerebral rSO 2 may provide insight and possibly serve as a predictor of ROSC and SHD.
Abstract 9462: Racial Disparities in Transcatheter and Surgical Aortic Valve Replacement Among Medicare Beneficiaries in the United States, 2012-2019
Authors: Aakriti Gupta, Makoto Mori, yun wang, Torsten Vahl, Tamim Nazif, Oyere K Onuma, Celina M Yong, Rahul Sharma, Ajay J Kirtane, John K Forrest, Isaac George, Susheel K Kodali, Joanna Chikwe, Arnar Geirsson, Raj Makkar, Martin Leon, Harlan M Krumholz
Journal: Circulation (2022)

Background: There are concerns that transcatheter or surgical aortic valve replacement (TAVR/SAVR) procedures are preferentially available to White patients. Methods: We stratified Medicare beneficiaries hospitalized with principal diagnosis of AS between 2012 and 2019 (n=299,976) by self-reported race/ethnicity (Black, Hispanic, Asian, Native American, and White). We evaluated AVR rates within 6 months of index hospitalization and associated procedural outcomes, including 30-day and 1-year mortality, and discharge disposition. We fitted Cox-proportional hazard models for outcomes, adjusting for demographics and comorbidities using race/ethnicity subgroup-specific-stabilized inverse probability weights. Results: Within 6 months of an index admission for AS, 86.8% (122,457 SAVR; 138,026 TAVR) patients underwent AVR. Overall, compared with White people, Black [HR 0.87 (0.85-0.89)], Hispanic [0.92 (0.88 - 0.96)], and Asian [0.95 (0.91 - 0.99)] people were less likely to receive AVR (Figure). Among patients who were admitted emergently/urgently, White patients (41.1%, 95% CI 40.7-41.4) had a significantly higher AVR rate within 6 months compared with Black (29.6%, 95% CI 28.3-30.9), Hispanic (36.6%, 95% CI 34.0-39.3), and Asian patients (35.4%, 95% CI 32.3-38.9). AVR rates increased annually for all race/ethnicities. There were no significant differences in 30-day or 1-year mortality by race. Black people were significantly more likely to be discharged to a facility compared with others. Conclusion: Within 6 months of AS admission, AVR rates are lower for Black, Hispanic, and Asian people compared with White people. These race-based differences in ultimate treatment of AS likely represent complex issues across the diagnosis and management of AS, warranting a comprehensive reassessment of the entire care spectrum for disadvantaged populations.
Abstract 9744: Declining Relative Use of Mitral Valve Repair in Australia Despite Superior Outcomes: A Statewide Population-linkage Study
Authors: Yeu-Yao Cheng, Matthew Wei Shun Shun, Vijayatubini Vijayarajan, Arielle Hsu, Karice HYUN, David Brieger, Vincent Chow, Leonard Kritharides, Austin Chin Chwan Ng
Journal: Circulation (2022)

Introduction: Mitral valve (MV) repair (MVr) has superior survival outcomes to MV replacement (MVR) for primary MV diseases. MVr cases has increased in other developed nations but is unknown in Australia. We assessed temporal trends in the total and relative MVr volume and compared MVr and MVR outcomes over 17 years. Method: Patients who had isolated MV surgery (MVSx) between 2001-2017 were identified from the New South Wales statewide Admitted Patient Data Collection registry. Mortality outcome was tracked to Dec 2018. Results: A total of 5693 patients (MVr: n=2020 [35%]; mechanical MVR: n=1656 [29%]; bioprosthetic MVR: n=2017 [35%]) were identified; median age [interquartile range] were 67y [59-75y] vs 64y [55-71y] vs 75y [68-80y], respectively (all P&lt;0.001). Median follow-up for the cohort was 6.3yrs. Annual MVSx cases increased over the study period but relative use of MVr declined from 44% (110/252 MVSx) in 2002 to 27% (165/601 MVSx) in 2017 (Fig1). Crude in-hospital and 1-yr mortality steadily declined for all groups between 2001 and 2017. MVr had the best outcome, with 1.2% in-hospital, 2.5% 1-yr, and 21.6% total cumulative mortality. Compared to MVr, after adjusting for age, sex, referral source, and comorbidities, the adjusted hazard ratios for long-term mortality were 1.41 (95% confidence interval [CI]=1.24-1.61) for mechanical MVR and 1.73 (95% CI=1.53-1.95) for bioprosthetic MVR (Fig 2). Conclusion: In this statewide Australian cohort study, relative use of MVr decreased over 17 years and are lower than reported by other international studies, despite having superior outcome compared to MVR. Factors driving the relatively low use of MVr should be explored.
Abstract 9843: Dynamic Importance of Genomic and Nongenomic Risk Factors for Coronary Artery Disease Over the Life Course
Authors: Sarah Urbut, So Mi J Cho, Sara Haidermota, Anthony A Philippakis, AKL FAHED, Pradeep Natarajan
Journal: Circulation (2022)

Introduction: Current cardiovascular risk models are limited by fixed window estimates of risk rather than lifetime trajectories. We create a novel framework to understand the time-varying profiles of genomic and non-genomic risk factors over the life span. Methods: We examine 325,948 individuals from the UK Biobank (UKB) (57% female, enrollment age 40-70 years, mean follow-up 11.9 years) with baseline clinical risk factors, composite Pooled Cohort Equations (PCE), and coronary artery disease (CAD) polygenic risk score (PRS). We compare Cox hazard ratios (HR) and the proportion of variation explained (PVE) at each age of enrollment. We extend analyses to a younger cohort of 3,821 individuals from the Framingham Health Study (FHS) Offspring Cohort, (51% female, enrollment ages 18-57, mean follow-up 35.1 years). Results: Results: HR and PVE of CAD PRS are greater early in life with HR 2.47, [95% CI 2.45-2.50] at age 40 to HR 1.67 [1.64,1.70] at age 70 in UKB; PVE of 7.8% to 2.3% in UKB. Parallel results were observed in FHS (Fig 1A-C) earlier in the life span. While the variation in lifetime risk increases with time, the HR for single risk factors estimated at each age are dynamic. The PCE, via inclusion of age, absorb much of this variation. Reclassification of intermediate 10-year PCE risk (7.5-19.9%) using PRS is most informative in younger individuals. In the UKB, the top-quintile of PRS, when compared to PCE alone, accurately predicts more individuals under age 55 (1108 versus 844) who ultimately develop CAD, but loses superiority over age 55 (Fig. 1D). Conclusions: Depending on when the question is asked, the HR of CAD of both genomic and non-genomic risk factors changes dramatically, with PRS demonstrating superiority early on. Our novel framework incorporates time-varying effects in portraying risk trajectory rather than fixed-window estimates. We show that polygenic scores also predict lifetime risk of disease early on rather than predicting only early-onset disease.
Abstract 9836: Variability of FXI and Relationship With Other Coagulation Factors - Sex Specific Differences and Impact of Diabetes Mellitus
Authors: Rolf P Kreutz, Joseph Ipe, Todd Skaar
Journal: Circulation (2022)

Introduction: Novel anticoagulants targeting inhibition of Factor XI (FXI) are in clinical development and may have lower adverse bleeding risk compared to FX inhibitors. Population based preclinical studies have shown lower risk of stroke in patients with lower levels of FXI. We sought to examine the relationship of FXI with other coagulation factors and prothrombotic markers in a cohort of patients with cardiac risk factors or established cardiovascular disease. Hypothesis: FXI activity is associated with alterations of other coagulation factors. Methods: Plasma samples from subjects enrolled in a cardiovascular biobank (n=418) were analyzed by multiplex assay for FXI, FXII, FXIII, prothrombin, PAI-1, tPA, fibrinogen, antithrombin, c-reactive protein. Results: Increasing quintiles of FXI were associated with increases in fibrinogen, antithrombin, c-reactive protein, FXIII, and PAI-1, but decreases in prothrombin and FXII (p&lt;0.001). FXI levels were higher in women than men (149±54 vs. 134±48; p&lt;0.01) and in patients with diabetes mellitus (150±50 vs. 139±52; p&lt;0.05). In patients with subsequent spontaneous major bleeding during follow up (n=10), FXI was not significantly different from those without bleeding events (p=0.41). Conclusions: FXI activity may exhibit sex specific differences, and FXI activity may be increased in patients with diabetes, which is a strong risk factor for myocardial infarction and stroke. FXI activity is closely tied to activity of various markers of thrombosis and clotting factors. Future studies are warranted to examine effects of FXI inhibition on other coagulation factors.
Abstract 9382: Reperfusion Delays and Outcomes Among ST-Segment-Elevation Myocardial Infarction Patients With and Without Cardiogenic Shock
Authors: Andrew F Kochan, Terry Lee, Nima Moghaddam, Grace Milley, Joel Singer, John A CAIRNS, Graham C Wong, Christopher Fordyce
Journal: Circulation (2022)

Introduction: Mortality remains high among STEMI patients with cardiogenic shock (CS), and rapid reperfusion has been shown to improve outcomes. However, the comparative benefits of shorter reperfusion times among STEMI patients with and without CS is unclear. Hypothesis: STEMI patients presenting with CS would have significantly greater increases in mortality and MACE as FMC-to-device time increased compared to non-CS patients. We hoped to identify a FMC-to-device time threshold below which outcomes were optimized for CS and non-CS patients. Methods: We performed a retrospective analysis using prospective data from the Vancouver Coastal Health Authority STEMI registry. We included all patients with STEMI who received PCI between January 1, 2010, and December 31, 2020. Patients were stratified based the presence of CS at the time of admission and assessed for the primary outcome of in-hospital mortality and the secondary outcome of an in-hospital major adverse cardiovascular event (MACE), defined as a composite of the first occurrence of mortality, cardiac arrest, heart failure, ICH/CVA/Stroke or reinfarction. Logistic regression was used to estimate the relationships between FMC-to-device time and the primary and secondary outcomes in the CS and non-CS groups. Results: 2929 consecutive STEMI patients were included, of whom 9.4% (n= 275) had CS. Median FMC-to-device time was 113.5 (IQR 93.0-145.0) minutes for CS patients and 103.0 (IQR 85.0- 130.0) minutes for non-CS patients. CS patients were more likely to have FMC-to-device times above guideline recommendations (76.6% vs. 54.1%, p &lt;0.001) compared to non-CS patients. Between 60 and 90 minutes, for each 10-minute increase in FMC-to-device time, mortality for STEMI patients with CS increased by 5-8%, while for non-CS patients it increased by less than 0.5%. Compared to non-CS patients, those with CS had higher incidences of mortality (41.1% vs. 1.9%, p &lt;0.001) and MACE (81.1% vs. 19.4%, p &lt;0.001). Conclusions: Among STEMI patients undergoing primary PCI, reperfusion delays among CS patients are associated with significantly worse outcomes compared to non-CS patients. Strategies to reduce FMC-to-device times for STEMI patients specifically presenting with CS are needed.
Abstract 9799: Financial Status, Fatalism and Self-Care of Cardiovascular Disease Risk Factors Among Rural Adults Living in Socioeconomically Distressed Areas
Authors: Dustin Hodges, Martha J Biddle, Misook L Chung, Frances J Feltner, Terry A Lennie, Jennifer Miller, Gia Mudd Martin, Jennifer Smith, Jiarong R Wu, Debra K Moser
Journal: Circulation (2022)

Background: Adults with fewer financial resources often have poor self-care. Fatalism is a belief that events in life are determined by outside forces. Rural adults commonly have fewer financial resources than urban dwellers and are often stereotyped as fatalistic about their health. Our aim was to determine whether fatalism mediates the association of financial status with cardiovascular disease (CVD) self-care in rural adults in economically distressed areas. Hypothesis: We hypothesized that those with fewer financial resources would have poorer self-care and fatalism would mediate this relationship. Methods: We enrolled 1118 adults (mean age 53 ± 15 years; 75.6% female) at risk for CVD. Financial status was reflected by individuals’ perceptions of how well they made “ends meet” with their financial resources (i.e., more than enough, enough, or not enough to make ends meet), fatalism by CVD-Fatalism Instrument, and self-care of CVD risk factors by Medical Outcomes Study-Specific Adherence Scale. We used conditional process analysis with PROCESS macro and 5000 bootstrap samples. Results: Financial status was associated directly with self-care. Those with with not enough to make ends meet (C' = -3.51, p = .003) and those with enough (C' = -1.57, p = .016) compared to those with more than enough had worse self-care. Fatalism was associated with self-care. Those hose with higher levels of fatalism had worse self-care (b = -1.78, p = .001). Financial status was indirectly associated with self-care through fatalism. Compared to those with more than enough, those with not enough (indirect effect = -.269, CI = -.609, -.021) and enough (indirect effect = -.182, CI = - .376, -.041) had higher fatalism levels and thus worse self-care. Conclusion: Poor financial status drives fatalism in rural dwellers, which in turn results in poor self-care.
Abstract 9515: Cariporide, a Selective Na+-H+ Exchange Inhibitor, Enhances Cardiac Positive Inotropic and Lusitropic Responses to Dobutamine in Heart Failure: Assessment by Pressure-Volume Analysis
Authors: Che Ping Cheng, Tiankai Li, Xiaowei Zhang, Zhi Zhang, David X Zhao, David M Herrington, Dalane W Kitzman, Heng-Jie Cheng
Journal: Circulation (2022)

Background: Inability of failing hearts to respond to positive inotropic agents such as dobutamine (DOB) represents a major clinical problem. We have shown previously that in addition to intracellular acidosis, various signaling pathways such as endothelin-1 and angiotensin II also activate cardiac Na + -H + exchange (NHE). In heart failure (HF), increased stimulation of NHE decreases myocardial calcium sensitivity. We hypothesized that blocking NHE with cariporide (CAR), a NHE-1-selective inhibitor, may improve β-adrenergic inotropic responsiveness in HF and enhance left ventricle (LV) positive inotropic and lusitropic responses of DOB. Methods: We compared the effect of clinically relevant doses of CAR (3.5 μg/kg, iv) on LV functional performance and LV contractile response to DOB (6 μg/kg/min, iv, 10 min) in 6 instrumented, conscious dogs after pacing-induced HF. LV contractile performance was measured by pressure (P)-volume (V) analysis. Animals received DOB first. After stopping DOB for 30 minutes, both DOB and CAR were infused. Results: After HF, DOB caused a 17% increase in E ES (5.3 ±1.5 vs 4.4±0.8 mmHg/ml), a16% increase in M SW (53.8±4.9 vs 45.3±3.7 mmHg), and an 11% decrease in the time constant of LV relaxation (τ) (40.4±2.6 vs 45.8±2.5 ms). DOB followed by CAR resulted in significantly greater effects with a 42% increase in E ES (6.1±2.3 vs 4.3±1.9 mmHg/ml) and a 37% increase in M SW (61.4±5.9 vs 45.1±3.2 mmHg), and a 23 % decrease in τ (34.1±3.6 vs 44.5±2.4 ms). Compared with DOB alone, DOB plus CAR caused no significant changes in heart rate (126±11 vs 130±12 bpm) and LV end-systolic P (110±8.6 vs 112±6.5 mmHg), but significantly decreased mean left atrial P (27.2±5.0 vs 32.9±5.4 mmHg), and increased stroke volume (32%, 13.3±1.7 vs 10.1±2.7 ml). DOB plus CAR also produced about 28% increased LV mechanical efficiency, measured as the ratio of stroke work to total P-V area (0.59±0.15 vs 0.46±0.17) ( p &lt;0.05). Conclusions: In pacing-induced HF, Na + -H + exchange inhibition by cariporide enhances LV positive inotropic and lusitropic responses to DOB. This suggests that combination therapy with intravenous cariporide and DOB may be appropriate in HF, thus providing a potential method of enhancing β-adrenergic responsiveness of the failing myocardium.
Abstract 9614: Association Between Myocardial Contraction Fraction and Heart Failure Subtypes in the Multi-Ethnic Study of Atherosclerosis (MESA)
Authors: Alexandria J Sutton, Haiying Chen, Marwah Abdalla, Daichi Shimbo, Joao A Ac Lima, Dalane W Kitzman, Alain G Bertoni
Journal: Circulation (2022)

Introduction: Myocardial contraction fraction (MCF) is a non-ejection fraction volumetric measure of myocardial shortening which has been associated with incident heart failure (HF) including in the Multi-Ethnic Study of Atherosclerosis (MESA) cohort. However, less is known regarding MCF’s prediction of HF subtypes. Methods: This analysis included men and women aged 45-84 free of clinical cardiovascular disease who underwent cardiac magnetic resonance imaging (cMRI) during the baseline MESA examination and who had data regarding incident adjudicated definite or probable HF events. MCF was calculated using cMRI measurements and defined as the ratio of stroke volume to myocardial volume. HF subtypes were divided into HF with ejection fraction (EF) &lt; 50% (HF EF &lt; 50%, including HF with reduced EF (EF ≤ 40%) and HF with mildly reduced EF (EF 41-49%) and HF with preserved EF (HFpEF, EF ≥ 50%). Cox proportional hazards regression was used to examine the association between MCF and incident HF subtype per decile increase in MCF. Event time was defined as time of first defined HF subtype, and censoring occurred at death or end of follow-up. After an incident HF event, participants were not at risk for another HF subtype. Covariates adjusted for were age, gender, race-ethnicity, education, body-mass index, tobacco and alcohol use, systolic blood pressure (BP), diabetes, physical activity, total cholesterol, and BP and lipid lowering drug use. Results: Among 4,983 participants (mean age 61, 52% female, 61% non-White) over a maximum of 18 years follow-up, there were 275 incident HF events (142 HF EF &lt; 50%, 113 HFpEF, 20 unknown EF). MCF differed across HF status (p&lt;0.001) . Participants without incident HF had a higher mean MCF (0.65) compared to HFpEF (0.62), HF EF &lt; 50% (0.53), and unknown EF (0.52). The adjusted risk of any HF was reduced (HR 0.86, 95% CI 0.82, 0.91) per decile increase of MCF. MCF was strongly associated with incident HF EF &lt; 50% (adjusted HR 0.80, CI 0.74, 0.86) but was not associated with HFpEF (adjusted HR 0.98, CI 0.91, 1.05). Conclusions: In a multi-ethnic cohort, increasing MCF is associated with a decreased risk of incident HF EF&lt;50%. MCF is not significantly associated with incident HFpEF, suggesting different etiologic pathways for these two HF subtypes.